The sequence of development of selected tumors from the initial event to overt cancer is being studied by the biopsy and serial sacrifice of animals, initiation-promotion bioassays using skin and liver models and serial karyotyping of target cells. Liver cancer histogenesis and histochemistry in monkeys, rats and mice are being compared. Significant differences were found as well as similarities. Karyotyping and initiation-promotion bioassays are being used to characterize possible mechanisms of cancer development for chemicals not demonstrated to be genotoxic, including ethionine, phthalates and formaldehyde.